Anorexia Nervosa (AN) is a life-threatening psychiatric disorder characterized by severe weight loss, distorted thinking about weight and appearance, and minimization of health and emotional problems. Typically, patients with AN also display a thinking style that is avoidant, rigid, and obsessive, which often limits the abilit of patients to respond to treatment. A growing body of literature demonstrates that this cognitive style is reflected in neuropsychological deficits in several domains, particularly, impaired set shifting (inflexibility), weak central coherence (exaggerated focus on detail to the neglect of the whole), and heightened sensitivity to reward and punishment. These inefficiencies may increase risk for AN given underlying brain abnormalities, and influence response to treatments. A comprehensive investigation of the neural basis of core cognitive inefficiencies in AN may suggest targets for cognitive treatments that enhance response to therapy and prevent relapse. There are a limited number of neuroimaging studies of cognitive function in AN. This application proposes a multimodal neuroimaging analysis, leveraging existing neuroimaging data collected with seed monies, to investigate the neural correlates of cognitive processes in AN. Twenty-four females with AN, ages 16-25, were previously recruited as part of an NIMH funded treatment trial. Structural and functional brain images were collected from these subjects at baseline, along with a matched group of 14 healthy female controls. This application requests funding needed to collect neuroimaging data from an additional 8 patients with AN, and to perform a comprehensive multimodal neuroimaging analysis of these existing data. State-of-the-art analyses will include multivariate pattern analysis of functional MRI acquired during standard tasks of set- shifting, central coherence, and reward processing. High resolution anatomical brain images will be subjected to a FreeSurfer analysis of regional volumes and cortical thickness throughout the brain. Diffusion tensor imaging data will be used to investigate white matter integrity throughout the brain, and tractography of fibers of interest. These analyses will contribute the most comprehensive assessment of the neural basis of neuropsychological processes in the existing AN literature. PUBLIC HEALTH RELEVANCE: Anorexia Nervosa is a life-threatening psychiatric disorder with risk of serious complications from self-imposed starvation. The typical thinking styles of patients with AN, such as cognitive rigidity, make it difficult for patients to benefit from therap. Response to treatment might be improved by better understanding the neural basis of these cognitive characteristics. This study augments an existing brain imaging dataset from patients with AN while performing cognitive tasks that tap into these thinking styles. This study will contribute state-of-the-art neuroimaging analyses of brain structure and function in AN, significantly advancing our understanding of this serious disorder.